Sclerostin antibodies in osteoporosis: latest evidence and therapeutic potential.

Sclerostin is an osteocyte-derived glycoprotein that inhibits Wnt/β-catenin signaling and activation of osteoblast function, thereby inhibiting bone formation. It plays a vital role in the regulation of skeletal growth. In adults, sclerostin secretion is modulated by skeletal loading (increased secretion with immobilization; less with weight bearing) and by hormonal/cytokine actions on the osteocyte. Sclerostin deficiency syndromes in humans and animals are characterized by high bone mass of normal quality. In animal models of osteoporosis, inhibition of sclerostin by monoclonal antibodies induces osteoblast activity and new bone formation, normalizing bone mass and improving bone architecture and strength. In recently completed clinical trials, anti-sclerostin antibody therapy results in marked increases in bone mineral density and rapid and substantial reduction in fracture risk. This review will focus on these recent studies and anticipate the role of anti-sclerostin therapy in the management of patients with osteoporosis.